摘要
背景:甲氨蝶呤(MTX)是抗风湿类疾病修饰药物中的代表药物。然而,氨甲喋呤常规治疗存在诸多局限性和副作用。 目的:为增强甲氨蝶呤治疗类风湿性关节炎的靶向能力和循环时间,研究了一种新型的经甘露糖修饰的甲氨蝶呤载人血清白蛋白纳米粒(MTX-M-NPs)给药系统。 方法:首先合成甘露糖羧酸,并在MTX-NPs表面进行修饰制备MTX-M-NPs。以药物脂质比、油水比、胆固醇或卵磷脂质量为自变量,采用中心复合设计(CCD)方法优化纳米颗粒的处方。平均粒径和包封效率为响应变量。计算不同配方的响应,利用响应面图、等高线图和数学方程将因变量和自变量联系起来,预测最优配方比例。通过共聚焦激光检测研究中性粒细胞对MTX-M-NPs的吸收。进一步,对静脉注射给Sprague-Dawley大鼠后的MTX-M-NPs进行药代动力学分析。 结果:成功研制了靶向给药系统。核磁共振和傅里叶变换红外光谱分析结果验证了该给药系统的成功制备。在此基础上,制备出粒径为188.17 +} 1.71 nm、包封率为95.55 +} 0.33%的MTX-M-NPs。MTX-M-NPs的细胞摄取明显高于MTX-NPs。药代动力学结果表明,MTX-M-NPs可延长MTX体内循环时间。 结论:该靶向给药系统为RA的治疗奠定了良好的基础。
关键词: 甲氨蝶呤,纳米给药系统,中心复合设计,处方优化,MTXM- NPs,自身免疫性疾病。
Current Medicinal Chemistry
Title:Preparation and Formulation Optimization of Methotrexate-loaded Human Serum Albumin Nanoparticles Modified by Mannose
Volume: 28 Issue: 24
关键词: 甲氨蝶呤,纳米给药系统,中心复合设计,处方优化,MTXM- NPs,自身免疫性疾病。
摘要:
Background: Methotrexate (MTX) is the representative drug among the disease- modifying anti-rheumatic drugs. However, the conventional treatment with MTX showed many limitations and side effects.
Objective: To strengthen the targeting ability and circulation time of MTX in the treatment of rheumatoid arthritis, the present study focused on developing a novel drug delivery system of methotrexate-loaded human serum albumin nanoparticles (MTX-NPs) modified by mannose, which are referred to as MTX-M-NPs.
Methods: Firstly, mannose-derived carboxylic acid was synthesized and further modified on the surface of MTX-NPs to prepare MTX-M-NPs. The formulation of nanoparticles was optimized by the method of central composite design (CCD), with the drug lipid ratio, oil-aqueous ratio, and cholesterol or lecithin weight as the independent variables. The average particle size and encapsulation efficiency were the response variables. The response of different formulations was calculated, and the response surface diagram, contour diagram, and mathematical equation were used to relate the dependent and independent variables to predict the optimal formula ratio. The uptake of MTX-M-NPs by neutrophils was studied through confocal laser detection. Further, MTX-M-NPs were subjected to assessment of the pharmacokinetics profile after intravenous injection with Sprague-Dawley rats.
Results: This targeting drug delivery system was successfully developed. Results from Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy analysis can verify the successful preparation of this drug delivery system. Based on the optimized formula, MTX-M-NPs were prepared with a particle size of 188.17 ± 1.71 nm and an encapsulation rate of 95.55 ± 0.33%. MTX-M-NPs displayed significantly higher cellular uptake than MTX-NPs. The pharmacokinetic results showed that MTX-M-NPs could prolong the in vivo circulation time of MTX.
Conclusion: This targeting drug delivery system laid a promising foundation for the treatment of RA.
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Cite this article as:
Preparation and Formulation Optimization of Methotrexate-loaded Human Serum Albumin Nanoparticles Modified by Mannose, Current Medicinal Chemistry 2021; 28 (24) . https://dx.doi.org/10.2174/0929867328666210118112640
DOI https://dx.doi.org/10.2174/0929867328666210118112640 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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